Subcutaneous Infusion of DNA-Aptamer Raised against Advanced Glycation End Products Prevents Loss of Skeletal Muscle Mass and Strength in Accelerated-Aging Mice
Yusaku Mori,
Makoto Ohara,
Michishige Terasaki,
Naoya Osaka,
Hironori Yashima,
Tomomi Saito,
Yurie Otoyama-Kataoka,
Takemasa Omachi,
Yuichiro Higashimoto,
Takanori Matsui,
Tomoyasu Fukui,
Sho-ichi Yamagishi
Affiliations
Yusaku Mori
Anti-Glycation Research Section, Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Shinagawa, Tokyo 142-8555, Japan
Makoto Ohara
Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Shinagawa, Tokyo 142-8555, Japan
Michishige Terasaki
Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Shinagawa, Tokyo 142-8555, Japan
Naoya Osaka
Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Shinagawa, Tokyo 142-8555, Japan
Hironori Yashima
Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Shinagawa, Tokyo 142-8555, Japan
Tomomi Saito
Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Shinagawa, Tokyo 142-8555, Japan
Yurie Otoyama-Kataoka
Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Shinagawa, Tokyo 142-8555, Japan
Takemasa Omachi
Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Shinagawa, Tokyo 142-8555, Japan
Yuichiro Higashimoto
Department of Chemistry, Kurume University School of Medicine, Kurume 830-0011, Fukuoka, Japan
Takanori Matsui
Department of Bioscience and Biotechnology, Fukui Prefectural University, Eiheiji 910-1195, Fukui, Japan
Tomoyasu Fukui
Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Shinagawa, Tokyo 142-8555, Japan
Sho-ichi Yamagishi
Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Shinagawa, Tokyo 142-8555, Japan
We have developed DNA aptamers that can inhibit the toxic effects of advanced glycation end products (AGE-Apts). We herein evaluated the effects of AGE-Apts on muscle mass and strength in senescence-accelerated mouse prone 8 (SAMP8) mice. Eight-month-old male SAMP8 mice received subcutaneous infusion of control DNA aptamers (CTR-Apts) or AGE-Apts. Mice in an age-matched senescence-accelerated mouse resistant strain 1 (SAMR1) group were treated with CTR-Apts as controls. The soleus muscles were collected after the 8-week intervention for weight measurement and histological, RT-PCR, and immunofluorescence analyses. Grip strength was measured before and after the 8-week intervention. AGE-Apt treatment inhibited the progressive decrease in the grip strength of SAMP8 mice. SAMP8 mice had lower soleus muscle weight and fiber size than SAMR1 mice, which was partly restored by AGE-Apt treatment. Furthermore, AGE-Apt-treated SAMP8 mice had a lower interstitial fibrosis area of the soleus muscle than CTR-Apt-treated SAMP8 mice. The soleus muscle levels of AGEs, oxidative stress, receptor for AGEs, and muscle ring-finger protein-1 were increased in the CTR-Apt-treated mice, all of which, except for AGEs, were inhibited by AGE-Apt treatment. Our present findings suggest that the subcutaneous delivery of AGE-Apts may be a novel therapeutic strategy for aging-related decrease in skeletal muscle mass and strength.
